Evidence map›Paper›PMID 41206865›Full record

ArticleCell reports2025

Inducing ferroptosis to impede metastasis by inhibiting the calcium channel TRPC6.

Boris S Dimitrov, Dimpi Mukhopadhyay, Hira Lal Goel, Emmet R Karner, Christi A Silva, Ayush Kumar, Cornelia Peterson, Mengdie Wang, Arthur M Mercurio

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Boris S DimitrovDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Dimpi MukhopadhyayDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Hira Lal GoelDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Emmet R KarnerDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Christi A SilvaDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Ayush KumarDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Cornelia PetersonDepartment of Comparative Pathobiology, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 05136, USA.
Mengdie WangDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Arthur M MercurioDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA. Electronic address: arthur.mercurio@umassmed.edu.

Funding

Mechanisms and Therapy of Radiation Resistance in Breast CancerR01CA285607 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Arthur M Mercurio · 2024 to 2026
$1.6M
Novel Therapeutic Approaches for Aggressive Prostate CancerR01CA276863 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Arthur M Mercurio · 2023 to 2026
$1.5M
Investigating the Role of MYC in Meibomian Gland OncogenesisK01OD034451 · OD · TUFTS UNIVERSITY BOSTON · PI Cornelia Ward Mary Peterson · 2024 to 2026
$380k
NCI NIH HHS R01 CA276863NCI NIH HHS R01 CA285607NIH HHS K01 OD034451
6 · The paper itself

Abstract

We investigated a potential function of transient receptor potential cation channel 6 (TRPC6) in enabling breast cancer cells to resist stimuli that induce ferroptosis. A minority population of quiescent cells was isolated from triple-negative breast cancer (TNBC) cell lines that exhibit increased TRPC6 expression and resistance to ferroptosis compared to proliferating cells. These quiescent cells are also more metastatic than the proliferating cells, supporting the hypothesis that metastasis requires the ability of cells to evade ferroptosis. In pursuit of the mechanism, we discovered that the ability of TRPC6 to repress c-Myc is essential because its repression sustains levels of glutathione that are sufficient to impede ferroptosis. Importantly, treatment of TNBC cells with a TRPC6 inhibitor reduces metastasis significantly, an effect that is mitigated by a ferroptosis inhibitor. These results indicate that a sub-population of TNBC cells characterized by TRPC6 expression has the potential to form metastases by evading ferroptosis.

Indexed as

FerroptosisTriple Negative Breast NeoplasmsTRPC6 Cation ChannelAnimalsCell Line, TumorFemaleGlutathioneHumansMiceNeoplasm MetastasisProto-Oncogene Proteins c-mycGlutathioneProto-Oncogene Proteins c-mycTRPC6 Cation ChannelTRPC6 protein, humanbreast cancercancerCP: cancerferroptosisglutathionemetastasisTRPC6

Identifiers

PMID41206865
PMCPMC12746528

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.